Current Topics in Medicinal Chemistry

Allen B. Reitz
Fox Chase Chemical Diversity Center, Inc.
Doylestown, PA
USA

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Structure-based Virtual Screening Approaches in Kinase-directed Drug Discovery

(E-pub Ahead of Print)

Author(s): Dávid Bajusz, György G. Ferenczy, György M. Keserű.

Abstract:

Protein kinases are one of the most targeted protein families in current drug discovery pipelines. They are implicated in many oncological, inflammatory, CNS-related and other clinical indications. Virtual screening is a computational technique with a diverse set of available tools that has been shown many times to provide novel starting points for kinase-directed drug discovery. This review starts with a concise overview of the function, structural features and inhibitory mechanisms of protein kinases. In addition to briefly reviewing practical aspects of structure-based virtual screenings, we discuss several case studies to illustrate the state of the art in the virtual screening for type I, type II, allosteric (type III-V) and covalent (type VI) kinase inhibitors. With this review, we strive to provide a summary of the latest advances in the structure-based discovery of novel kinase inhibitors, as well as a practical tool to anyone who wishes to embark on such an endeavor.

Keywords: Drug Discovery, Kinase, Structure-based Virtual Screening, Inhibitor, Docking, DFG motif, Activation Segment, Hinge, Covalent Dockin

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Article Details

VOLUME: 17
Year: 2017
(E-pub Ahead of Print)
DOI: 10.2174/1568026617666170224121313
Price: $95